Sulphonamide compounds



' useful in azo dye. manufacture.

Patented Sept. 19, 1944 UNITED STATES PATENTOFFICE' su rnommnnn oomotmnsJames G. McNally and Joseph B. Dickey, Rochester, N. Y., assignors toEastman Kodak Company, Rochester, N. Y., a corporation of New Jersey NoDrawing.

pplication July 11, 1941,

Serial No. 401,972 13 Claims. (01. 260-556) In the prior artv referenceis made to the 3.5-dinitroaminobenzenesulphonamide compounds wherein oneor more of the hydrogen atoms of the amide'group may be there are foundcompounds which might appear to resemble our novel compounds in somerespects. However, such prior art compounds, rather than being thesulphonamide type are the sulphone type and are not as satisfactory asthe compounds of the present invention. While certain compoundscontaining the sulphonamide grouping in the molecule have been describedin'the prior art, such compounds have not been utilizable in dyemanufacture for various reasons such as the absence of a diazotizableamino group. It -is, therefore, apparent that the development ofaminoarylsulphonamide derivatives which overcome the disadvantages ofthe prior art and which are capable of use in the manufacture of azodyes,

as well as other industrial uses, is a highly desirable result,

This invention has for one object to provide new and improvedarylsulphonamide compounds and method of manufacture. Another object isto provide new sulphonamide compounds particularly A still furtherobject is to provide new compounds having not only a sulphonamide groupor substituted group therein, but also containing in the molecule a,diazotizable amino group. A still further objectis to provide novelintermediate compounds from which may be readily obtained the aforesaidcomsubstituted with certain substituent such as alkoxy alkyl or otheralkyl groupings.

Referring now to certain of the more general aspects of our invention,our arylamines may be broadly formulated as follows:

No NH:

1 SO1N wherein R1 and R2, for example, represent members selected fromthe group consisting of hydrogen, alkyl groups such as methyl, ethyl,propyl, butyl and the like, hydroxyl groups such a hydroxyethyl,dihydroxylpropyl, alkoxyalkyl groups such as methoxyethyl, ethoxyethyland the like, alkylene groups, cycloalkyl groups, aryl groups orhydro-derivatives of aryl groups, and Y preferably represents a nitrogroup, but may in certain instances represent a member selected from thegroup consisting of halogen, alkyl group, alkoxy group, or asulphonamide group. The amino compounds, in accordance .with thiinvention, may be prepared by halogenating, nitrating, or sulphonatingwith chlorosulphonic acid the necessary aryl compound and reacting withammonia or various amines, as desired. However, details novel compoundsmay be produced, as will be set forth in detail hereinafter, there arecertain of our novel sulphonamide derivatives which give of preferredoperation will be set forth hereincompounds having a general formula:

of the steps respecting the manufacture of cer- No,- -c1+msol NOQC:

I om II NO: NO Cl-FHNO: NOrQCl I 013 on! In No, NO:

-s- 1 NO NO 01+ 110 o and/or (PoClrl-Pch) ITIO: Cl+ammonis rim-Q4111,

N0 NH:

o=s=o N0 NH alkali v q alkylsul hate N o=l=o alkylha de, etc.

N0 NH:

; N Rl I I 0 3 R1 IIIO: I No: w No,- Cl+primsry amine N0-Ci 0l ll NH-R1N0: orssecondary amine NOQC] N01 N03 m NOr-QCi-l-NH: NOu-QNH:

= I O: I =0 NH-RI NH-R, No, no, -vm QQCl-FNHr NOQNH:

O= =0 I O: I =0 N-Ra NR:

(Nata-In the foregoing, for brevity R1 and R2 refer to the alkyl orother comparable group.)

While the preparation of certain of the starting materials employed isapparent from prior art disclosures, in view of the fact that ahalogenated derivative under Steps HI and V1 is particularly importantas an intermediate material, I will derivatives,- particularly withrespect to the 2-amino-3,5-dinitro compound. In the event it 1 to roomtemperature and is then warmed until is desired to produce the2,6-dinitro derivative EXAMPLE 1.Preparation of2-chloro-3,5-dinitrobenzene-sulphonyl chloride gm.2-chloro-3,5-dinitrobenzene sulphonic acid sodium salt are heated to150? for 16 hours with cc. chloro sulphonic acid. The product is pouredonto ice and then warmed to to dissolve the unchanged sodium2-chloro-3,5- dinitrobenzene sulphonic acid. The acid chloride isfiltered off, washed and dried. The. yield of product melting at101-103" is 80%.

After having obtained a satisfactory intermediate starting material suchmaterial or analogous halogenated derivative may be further used inaccordance with the above described equations for making the finalcompounds in accordance with the present invention, details respectingsuch further reaction being set forth as follows:

EXAMPLE 2.Preparation of Z-amino-3,5-dinitrobenzenesulphonamide One moleof finely divided 2-chlor-3,5-dinitrobenzenesulphonyl chloride is addedslowly to 10 moles iced ammonia water with vigorous stirring. Thereaction mixture is allowed to warm. slowly all of the product passesinto solution. Upon cooling, a. yellow crystalline mass separates whichis filtered, washed with water and dried. A good yield of2-amino-3,5-dinitrobenzenesulphonamide is obtained which melts at 255 C.

EXAMPLE 3.Preparation of N-ethyl-tj-dinitro-Z-chlorobenzene-I-sulphonamide 602 gm, of3,5'-dinitro-2-chlorobenzene-1-sulphonyl chloride are dissolved in 5 l.of acetone and the solution cooled to 10 C. With vigorous stirring, 592cc. ethylamine (33% in water, 4 moles) are added slowly over 2 hours,keeping the temperature of reaction at -5 C to --10 C. The mixture isthen stirred for 2-3 describe in detail the preparation of such halogenhours allowing the temperature to rise to 0 C. The mixture is thendiluted with 15 1. water and the precipitate'filtered oil. 565 gm. of N-ethyl-3,5-dinitro-2-chlorobenzene- 1 -sulphamide are obtained, meltingat 138-141 C. Analysis: Chlorine, calculated for CsHsNaSOcCl-11.50%;found 11.82%.

Similarly there may be prepared the following:

. Melting point N-methyl-3,5-dinitro-2-chlorobenzene- EXAMPLE 4.--,Preparation of N-hydroxyethyl-3,5-

dinitro-Z-aminobenzene-I-sulphonamide 53 gm. ofN-hydroxyethyl-3,5-dinitro-2-chlorobenzene-l-sulphonamide and 250 cc.concentrated ammonia (28%) are stirred at room temperature (25 0,approx.) for 3-4 hours until the solid no longer gives a test forhalogen. The

mixture is then heated cautiously on the steam bath to 90, diluted to 1liter with water, cooled and filtered. 41 gm. ofN-hydroxyethyl-3,5-dinitro-Z-aminobenzene-l-sulphonamide are obtained,melting at l75-6.

In a similar manner are prepared:

a Melting point N-methyl-3,5-dlnltro-2-aminobenzenel-sulphonamide 1'13-5 N-ethyl-3,5-dinitro-2-aminobenzenel-sulphonamide 148-50N-methoxyethyl-3,5-dinitro-2=amino- V benzene-l-sulphonamide 154- 6While 1 have described in particular the use of halogen derivatives, itis to'be understood that my novel compounds are not restricted to onesderived solely from this source. in the preparation of my compounds itis also possible to use alkali salts of certain starting materials orthe combination methods employing both alkali salts and halogenderivatives.

Still further examples of producing compounds in accordance with myinvention'are as follows:

EXAMPLE 5.Prepara.tion of 2-amino-3,5-dim'trobenzenediethylsulphonamideOne mole of the disodium salt of 2-amlno-3,5-dinitrobenzenesulphonaxnide is heated with 2.25

moles ethyl sulphate at reflux for 1 hour using methyl Carbitol orCellosolve as a solvent. Most of the solvent is distilled oil? underreduced pressure and water is added. The mixture is made alkaline withsodium hydroxide and filtered. The product is crystallized if desired.There is obtained an excellent yield of the amide melting at 136-138".In a similar manner there havebeen preparedZ-amino-3,5-dinitrobenzenedimethylsulphonamide;2-amino-3,5-dinitrobenzenedipropylsulphonamide;2-amino-3,5-dinltrobenzensulphondibutylamide;2-amino-3,5-dinitro-di-p-hydroxyethylamide, etc.

EXAMPLE 6.-Preparation of 2'-amino-3,5-dinitroethylbenzenesulphonamideby which my preferred dinitro compounds are produced. The aforesaid2-amino-3,5-dinitro compounds, as described, are particularly valuablecompounds for various uses. in dye manufacture, enabling the productionof shades of dyes not obtainable by other sulphonamide or sulphonecompounds. There are, however, certain isomers of the compoundsdescribed which, while not giving the same results or being capable ofall the uses of our preferred compounds, .are valuable compounds, andmay be produced and used in a manner somewhat comparable to that alreadydescribed. For example, these com- For example,

I pounds may be generically formulated as follows:

R1 \r- '--NH,

-N0a the meaning already wherein R1 and B: have assigned. 10 Forconvenience of consideration and conciseness of disclosure below we setforth in the form of equations, steps in the preparation of saidcompounds in a manner paralleling the precede ing description:

Q-oHmsoi nsmQ-m No, NO,

H-A N O:

No! NO:

III-A N0: N0:

, (PCla+POCl|) NaSO -Cl+HOSCl clso Gl O O NOa. NO:

IV-A NO: NO:

' NO: 1 O

alkali N O l 0 H l 45 alkyl sulphate am-ir-Qmn (Note-In the foregoing,for brevity R1 and Bi refer to the alkyl or other comparable group.)

VI-A

m halide, etc.

0 N0, N02- i H 01- 01+ Primary mine --a R -N nf Cl 0 g 0: 1) NO:

Becondary amine N-S o1 Y 4;

1 VII-A 1 H RrN-S CH-NHQ RrN-S NH1 4 v 4', 0 N0: 0 N02 QolhimmonlaNmsm-QNH,

Likewise in the preparation of these di-nitro sulphonamide compoundswherein the sulphonamide group is in a position para to the amino group,the compounds may be made from the halogen derivative, as for example,the chlorine derivative or alkali salts may be employed. The halogenderivative could be produced in a manner similar to the preparation setforth in Example 1.

. EXAMPLE 7.Prepa ration of 4-chloro-3,5-dinitrobenzene-sulph nylchloride 25 g. of sodium-4-chloro-3,5-dinitrobenzenesulphonic acid areheated to 150 for 16 hours with 30 cc. of chlorosulphonic acid and thenpoured onto ice. The mixture is warmed to 50 to dissolve the unchangedsulphonic acid. The acid chloride is filtered off, washed with water,and dried.

Having the halogen derivative it could be reacted with ammonia toproduce the amide in a manner analogous to Examples 2, 3, and 4. Thatis, having 4-chloro-3,5-benzenesulphonyl chloride this compound could bereacted with iced ammonia water with vigorous agitation to obtain4-amino-3,5-dinitrobenzenesulphonamide.

Or the aforesaid halogen compound(3,5-dinitro-4-chlorobenzene-l-sulphonyl chloride) insozene-l-sulphonamide, and N-methoxyethyl-3,5-

dinitro-4-aminobenzene 1 sulphonamide could be produced in a manneranalogous to the process used in Example 4.

Likewise the sodium salt may be employed in a, manner somewhatcomparable to the procedure already described, as may be apparent from aconsideration of'the following examples:

vExsmnuns 8.-Preparation of4-amino-3,5-dinitrobenzenediethylsulphonamide One mole of the disodiumsalt of 4-amino-3,5- dinitrobenzenesulphonamide is heated with 2.25moles of ethyl sulphate at reflux for 1 hour using methyl Carbitol orCellosolve as a solvent. Most of the solvent is distilled off underreduced pressure and water is added. The mixture is made alkaline withsodium hydroxide and filtered. The product is crystallized is desired.There is obtained an excellent yield of the amide. In a .similar mannerthere have been prepared 4- amino-3,5dinitrobenzenedimethylsulphonamide; 2 amino 3,5dinitrobenzenedipropylsulphonamide; 2-amino-3,5dinitrobenzenesulphondibutylamide;2-amino-3,5-dinitro-dis-hydroxyethylsulphonamide, etc.

EXAMPLE 9.Pre p aration of 4-amino-3,5-dinitroethylbenzenesulphonamide15 g. 'of 4-amino-3,5-dinitrobenzenesulphonamide monosodium saltdissolved in Carbitol are heated to refluxing with 10 g. of ethylsulphate. After 1 hour the reaction mixture is poured into water andmade alkaline with sodium hydroxide. The insoluble diethylamide isremoved by filtration and the filtrate is made acid with hydrochloricacid. The monoethylamide is recovered by filtration. ,Ethyl iodide maybe used in prepared by procedure apparent from the foregoing disclosure,areas follows:

3,5-dinitro 2 chlorobenzenesulphonbenzylamide,

M. P. 240-241 C.

3,5-dinitro 2-aminobenrenesulphonbenzylamide,

M. P. 217-218 C.

3,5-dinitro 2 aminobenzenesulphon-a-pyridylamide, M. P. 235-238 C.

3,5-dinitro 2 aminobenzenesulphoncyclohexylamide, M. P. 214-215 C.

3,5-dinitro 2 chlorobenzenesulphoncetylamide,

M. P. 98-100 C.

3,5-dinitro 2 aminobenzenesulphoncetylamide,

M. P; 142-150" C.

3,5-dinitro 2-chlorobenzenesulphon-p-hydroxyp-ethoxyethylamide, M. P.216-217 C.

3,5-dinitro Z-aminobenzenesuIphOn-B-hydrOxyp-ethoxyethylamide, M. P.181-183 C.

3,5-dintiro-2 chlorobenzenesulphonanilide, M. P. 177-179 C. y

3,5-dinitro 2-aminobenzenesulphonanilide, M. P.

3,5-dinitro 2 chlorobenzenesulphon-p-dimethylaminoanilide, M. P. 186-189C.

3,5-dinitro Z-aminObenzenesuIphon-p dimethylaminoanilide, M. P. 1'75-178C.

3,5-dinitro 2 chlorobenzenesulphontetrahydrofurfurylamide, M. P; 140-142C.

3,5-dinitro 2 aminobenzenesulphontetrahydro furfurylamide, M. P. -101 C.

In the foregoing examples specifically in place of the chlorinederivative we may employ the bromide or iodine derivative.

The compounds of our invention have a plural- 'ity of nitro groupsattached to the benzene nucleus as well as diazotizable amino groups andthe aforedescribed sulphonamide substituted amides are particularlyvaluable compounds. These compounds are superior to what might appear tobe similar sulphone compounds in that, for example, our compounds. areless acid, have better solubility, and other properties superior toprior art compounds.

It is, therefore, apparent from the foregoing that certain of thegeneric aspects of our invent tion are susceptible of some modification,hence, we do not wish to be restricted excepting insofar as isnecessitated by the prior art and the spirit of the appended claims.

What we claim and desire to be secured by Lette'rs Patent of the UnitedStates is:

1. The compound having the formula:

2. The compound having the formula:

NO: I

OzN NH:

O N NH:

4. The compound having the formula:

OgN NH:

H -N alkyl 5. A process for preparing a sulphonamido compound comprisingcondensing 2-chloro-3,5- dinitro-l-sulphonyl chloride with a primarymonoarnine selected from the group consistinfl of allqlamines,hydroxyalkylamines, alkoxyalkylamines, cyclohexylamine, aralkylamines o!the benzene series and arylamines of the benzene series, at atemperature below C.

6. A process for preparing a sulphonamido compound comprising condensing2-chloro-8,5- dinitro-l-sulphonyl chloride with a primary monoamineselected from the group consisting of alkylamines, hydroxyalkylamines,alkoxyalkylamines, cyclohexylamine, aralkylamines of the benzene seriesand arylamines of the benzene series. at a temperature below 0 C., andthen condensing the resulting sulphonamido compound with ammonia. '7. Aprocess for preparing a sulphonamido compound comprising condensing2-chloro-3,5- dinitro-l-sulphonyl chloride with ethylamine at atemperature below 0 C. I

8. A process for preparing a sulphonamido compound comprising condensing2-chloro-3,5-

dinitro-l-sulphonyl chloride with ethylamine, at a temperature below 0C., and then condensing the resulting2-ch1oro-3,5-dinitro-l-sulphonamido compound with ammonia.

-9. A process for preparing a sulphonamido compound comprisingcondensing 2-chloro-3,5- dinitro-l-sulphonyl chloride with methylamineat a temperature below 0 C.

10. A process for preparing a sulphonamido compound comprisingcondensing 2-chloro-3,5- dinitro-l-sulphonyl chloride with methylamine,at a temperature below 0 C., and then condensing the resulting2-chloro-3,5-dinitro-l-sulphonamido compound with ammonia.

11. A process for preparing a sulphonamido compound comprisingcondensing 2-chloro-3,5- dinitro-l-sulphonyl chloride with fi-methoxyethylamlne, at a temperatur below 0 C.

12. A process for preparing a sulphonamido dinitro-l-sulphonyl chloridewith p-methoxy ethylamine, at a, temperature below 0 C., and thencondensing the resulting 2-chloro-3,5-dinitro-l-sulphonamidc compoundwith ammonia.

13. A compound having the general formula:

ON NH:

wherein R1 represents a member selected from the group consisting ofhydrogen, an alkyl group. a hydroxyalkyl group, an alkoiwalkyl group, acyclohexyl group, an aralkyl group of the benzene series and an arylgroup of the benzene series.

JAMES G. McNALLY.

JOSEPH B. DICKEY.

Certificate of Correction Patent No. 2,358,465. September 19, 1944.

JAMES G. McNALLY ET AL. It is hereby cermfied that error appears in thegrinted sglescification of the abovemunbered patent requiring correctionas follows: age 2, t column, lines 3940, for that portion of Formula Vreading n s n v. o ll read 0 3 and that the said Letters Patent shouldbe read with this correction therein that the same may conform to therecord of the ease in the Patent Oifice.

Signed and sealed this'28th day of November, A. D. 1944.

[SEAL] LESLIE FRAZER,

Acting Commissioner of Patents.

